Monoclonal antibodies against cancer-specific molecules have been proved to be useful in cancer treatment (Harris, M. (2004). Lancet Oncol, 5, 292-302). In addition to successful examples of clinical application of the humanized or chimeric antibodies such as trastuzumab (Baselga, J. (2004). Oncology, 61, Suppl 2 14-21), rituximab (Maloney, D. G., et al. (1997). Blood, 90, 2188-95) and bevacizumab (Ferrara, N., et al. (2004). Nat Rev Drug Discov, 3, 391-400) for breast cancer, malignant lymphoma and colon cancer, a number of monoclonal antibodies against other molecular targets are in development and being evaluated their anti-tumor activities. These monoclonal antibodies are expected to provide a hope to patients having tumors that have no effective treatment. One of the other important issues for these monoclonal antibodies is achievement of selective therapeutic effects to cancer cells without severe toxicity due to their specific reaction to cells expressing target molecules (Crist, W. M., et al. (2001). J Clin Oncol, 19, 3091-102; Wunder, J. S., et al. (1998). J Bone Joint Surg Am, 80, 1020-33; Ferguson, W. S. and Goorin, A. M. (2001). Cancer Invest, 19, 292-315).
Among soft tissue sarcomas, osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma are sensitive to chemotherapy and these diseases can be well managed by chemotherapy. On the other hand, spindle cell sarcomas are resistant to chemo- and radiotherapy and patients with them usually exhibit poor prognosis. For synovial sarcoma (SS), surgical treatment is effective for patients at an early stage, but no effective therapeutic drug is available to those at an advanced stage. Hence, development of novel therapeutic modalities is expected to improve patients' prognosis better.
Genome-wide gene expression analysis in tumors provides the useful information to identify the new molecular targets for development of novel anticancer drugs and tumor markers. In previous study, the present inventors have analyzed gene-expression profile of several soft tissue sarcomas using genome-wide cDNA microarray consisting of 23,040 genes and demonstrated that Frizzled homologue10 (FZD10) (GenBank Accession NOs. AB027464 (SEQ ID NO:1) and BAA84093 (SEQ ID NO:2)) was up-regulated specifically and frequently in SSs (Nagayama, S., et al. (2002) Cancer Res, 62, 5859-66; and WO2004/020668). FZD10 gene product is a member of Frizzled family and a putative WNT signal receptor (Koike, J., et al. (1999). Biochem Biophys Res Commun, 262, 39-43). Further analysis showed that FZD10 is expressed specifically in SS, and at no or hardly-detectable level in other normal organs except the placenta, suggesting that therapeutics targeting this molecule would cause no or little adverse reaction (Nagayama, S., et al. (2002). Cancer Res, 62, 5859-66). RNAi experiments implicated that FZD10 was significantly involved in the tumor growth of SS (WO2006/013733). Furthermore, the present inventors generated the rabbit polyclonal antibody against the extracellular domain of FZD10 (FZD10-ECD), and found that this antibody had antitumor activity in mouse xenograft model of SS (Nagayama, S., et al. (2005). Oncogene, 24, 6201-12; and WO2005/004912). Together, the antibody therapy against FZD10 could be expected to improve the clinical outcome of SS.